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Effect of a PPAR-Alpha Agonist on the Age Related Changes in Myocardial Metabolism and Mechanical Function

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by National Institute on Aging (NIA).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00627653
First received: February 28, 2008
Last updated: February 18, 2009
Last verified: February 2009
History of Changes
  Purpose

The purpose of this study is to determine if treatment with a drug called fenofibrate, which is a PPAR-alpha agonist and controls how the heart metabolizes fats, will reverse the age-related decline in cardiac fat metabolism and mechanical function.


Condition Intervention
Cardiovascular Diseases
 Drug: fenofibrate

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: PET (Positron Emission Tomography) Detection of the Effects of Aging on the Human Heart (Aim #2 Effect of a PPAR-Alpha Agonist on the Age Related Changes in Myocardial Metabolism and Mechanical Function)

Resource links provided by NLM:

Drug Information available for: Fenofibrate
U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • Shift in Myocardial substrate utilization in aging hearts [ Time Frame: After the day-30 PET scan ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Increased left ventricular function due to shift in substrate use in aging hearts [ Time Frame: After the day-30 PET scan ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2005
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: fenofibrate
148mg daily for 30 days
Other Name: Lofibra; TriCor

Detailed Description:

In older Americans, cardiovascular disease is the leading cause of death and disability. It has been shown recently that with aging the human heart exhibits a decline in myocardial fatty acid utilization (MFAU) and oxidation (MFAO) and that these metabolic changes are paralleled by a decline in mechanical function. It has also been shown that peroxisome proliferator activated receptor alpha (PPAR-alpha) activates the expression of the genes encoding enzymes involved in mitochondrial fatty acid transport and oxidation. There is both indirect and direct evidence that PPAR-alpha-mediated responses decrease with age. Consequently, we hypothesize that changes in fatty acid in the aging heart may be mediated, at least in part, via a decline in PPAR-alpha-mediated responses. Thus, administration of a PPAR-alpha agonist to older humans will result in a shift in cardiac fatty acid metabolism to that more closely seen in younger humans and this shift will be paralleled by an improvement in cardiac mechanical function.

To prove or disprove this hypothesis, we will determine, in aged and young healthy volunteers, whether stimulation of PPAR-alpha using the partial agonist, fenofibrate, shifts myocardial substrate utilization by increasing MFAU and MFAO, and whether these changes are associated with an increase in left ventricular function. Study participants will have 4 clinic visits, each lasting approximately 5 hours.

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 60-75 or 21-35
  • Normal glucose tolerance test
  • Normal plasma fasting lipid panel (fasting total cholesterol less than 220 mg/dL)
  • Normal rest/stress echocardiogram
  • BMI (body mass index) less than 30 kg/m2
  • Must be sedentary (active, but do not engage in regular exercise or jobs that require strenuous exertion)

Exclusion Criteria:

  • Coronary artery disease
  • High blood pressure
  • Current smoker
  • Diabetes mellitus
  • Cardiovascular disease (signs and symptoms of any kind)
  • Pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00627653

Locations
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Sponsors and Collaborators
National Institute on Aging (NIA)
Investigators
Principal Investigator: Robert Gropler, MD Washington University in St. Louis
  More Information

Publications:

Responsible Party: Robert Gropler, MD, Washington University in St Louis
ClinicalTrials.gov Identifier: NCT00627653     History of Changes
Other Study ID Numbers: AG0093, ROI AG15466
Study First Received: February 28, 2008
Last Updated: February 18, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
PPAR
PET study
heart metabolism

Additional relevant MeSH terms:
Cardiovascular Diseases
Fenofibrate
Hypolipidemic Agents
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013